Mastrianni J A, Capellari S, Telling G C, Han D, Bosque P, Prusiner S B, DeArmond S J
Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco 94143-0506, USA.
Neurology. 2001 Dec 26;57(12):2198-205. doi: 10.1212/wnl.57.12.2198.
To describe the clinical and neuropathologic profile and determine the strain characteristics of familial Creutzfeldt-Jakob disease (fCJD) caused by a point mutation of the PRNP gene at codon 210 that results in a valine-to-isoleucine substitution in the prion protein (PrP).
The clinicopathologic features of four individuals from the United States who died of fCJD(V210I) were compared. Transgenic (Tg) mice expressing a chimeric human-mouse PrP transgene were inoculated with brain extracts from three fCJD(V210I) cases, sporadic CJD (sCJD), fCJD(E200K), and fatal familial insomnia (FFI), to compare prion strain characteristics.
The clinicopathologic profile of fCJD(V210I) was variable among cases but shared similarities with sCJD. The pattern of PrP(Sc) deposition in the brains of Tg mice was similar to that caused by sCJD but different from that associated with fCJD(E200K) or FFI.
Each of these prion diseases is characterized by a rapidly progressive dementia with myoclonus, periodic complexes on EEG, and spongiform change without PrP plaque deposition in the brain. The occurrence of a different PrP(Sc) phenotype with each PRNP mutation argues that each respective amino acid sequence substitution produces a different prion strain.
描述由朊蛋白基因（PRNP）密码子210处点突变导致朊蛋白（PrP）中缬氨酸替换为异亮氨酸所引起的家族性克雅氏病（fCJD）的临床和神经病理学特征，并确定其毒株特性。
比较了来自美国死于fCJD（V210I）的4例患者的临床病理特征。用3例fCJD（V210I）病例、散发性克雅氏病（sCJD）、fCJD（E200K）和致死性家族性失眠症（FFI）的脑提取物接种表达嵌合人-鼠PrP转基因的转基因（Tg）小鼠，以比较朊病毒毒株特性。
fCJD（V210I）的临床病理特征在病例间存在差异，但与sCJD有相似之处。Tg小鼠脑中PrP（Sc）沉积模式与sCJD引起的相似，但与fCJD（E200K）或FFI相关的不同。
这些朊病毒疾病均以快速进展性痴呆伴肌阵挛、脑电图周期性复合波以及脑内无PrP斑块沉积的海绵状改变为特征。每种PRNP突变出现不同的PrP（Sc）表型表明，每种相应的氨基酸序列替换产生不同的朊病毒毒株。
